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PMID: 18356571 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Conditional stabilization of beta-catenin expands the pool of lung stem cells.

Stem cells (Dayton, Ohio) ·Vol. 26 ·No. 5 ·2008-05-00 ·Pages 1337-46

Reynolds SD, Zemke AC, Giangreco A, Brockway BL, Teisanu RM, Drake JA, Mariani T, Di PY, Taketo MM, Stripp BR

Abstract

Maintenance of classic stem cell hierarchies is dependent upon stem cell self-renewal mediated in part by Wnt/beta-catenin regulation of the cell cycle. This function is critical in rapidly renewing tissues due to the obligate role played by the tissue stem cell. However, the stem cell hierarchy responsible for maintenance of the conducting airway epithelium is distinct from classic stem cell hierarchies. The epithelium of conducting airways is maintained by transit-amplifying cells in the steady state; rare bronchiolar stem cells are activated to participate in epithelial repair only following depletion of transit-amplifying cells. Here, we investigate how signaling through beta-catenin affects establishment and maintenance of the stem cell hierarchy within the slowly renewing epithelium of the lung. Conditional potentiation of beta-catenin signaling in the embryonic lung results in amplification of airway stem cells through attenuated differentiation rather than augmented proliferation. Our data demonstrate that the differentiation-modulating activities of stabilized beta-catenin account for expansion of tissue stem cells.

MeSH Terms
Animals Bronchi/pathology Cell Count Cell Differentiation Cell Proliferation Cilia/ultrastructure Epithelial Cells/cytology,ultrastructure Lung/cytology,embryology Mice Phenotype S Phase Signal Transduction Stem Cells/cytology,metabolism,ultrastructure Thermodynamics Wound Healing beta Catenin/metabolism
Chemicals
beta Catenin
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Reynolds Susan D
Center for Lung Regeneration, Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Zemke Anna C
Giangreco Adam
Brockway Brian L
Teisanu Roxana M
Drake Jeffrey A
Mariani Thomas
Di Peter Y P
Taketo Mark M
Stripp Barry R
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Article Info
Journal
Stem cells (Dayton, Ohio)
Abbr.
Stem Cells
ISSN
1549-4918
DOI
10.1634/stemcells.2008-0053
Published
2008-05-00
Epub
2008-00-20
Pages
1337-46
Language
English
Region
United States
NLM ID
9304532
PMCID
PMC2773682
Subset
IM
Grants
NHLBI NIH HHS · R01 HL090146 · United States
NHLBI NIH HHS · R01 HL090146-02 · United States
NHLBI NIH HHS · R01 HL091938 · United States
External Links
PubMed source DOI: 10.1634/stemcells.2008-0053 PMC Full Text View journal details
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